PAF-induced bronchial hyperresponsiveness in the rabbit: contribution of platelets and airway smooth muscle.
1. Aerosol administration of platelet activating factor (PAF) to normal rabbits induced an enhanced airway responsiveness to inhaled histamine, 6 and 24 h after exposure. Following exposure to bovine serum albumin (BSA) as the carrier molecule for PAF, there was an increase in airway responsiveness to histamine 6 h after challenge, although by 24 h this was not significantly different from the responsiveness of airways to histamine before BSA. 2. PAF-induced bronchial hyperresponsiveness at 24 h was associated with a substantial increase in the number of neutrophils and mononuclear cells and a small, but significant increase in the number of eosinophils in the lungs as assessed by bronchoalveolar lavage. BSA exposure failed to alter the total number of cells in the lungs, although there was a significant increase in the number of neutrophils in the bronchoalveolar lavage fluid. 3. Selective platelet depletion with a guinea-pig anti-rabbit platelet serum inhibited PAF-induced bronchial hyperresponsiveness. In addition, there was an attenuation of PAF-induced airway inflammation in animals rendered thrombocytopenic. 4. The contractile potency to histamine, methacholine and carbachol was similar in intrapulmonary bronchi taken from rabbits exposed to an aerosol of BSA or PAF. Furthermore, the relaxant potency to the non-selective beta-adrenoceptor agonist isoprenaline, was unaltered in PAF-treated rabbits. In contrast, there was a 2.58 fold reduction in the relaxant potency to theophylline in rabbits exposed to PAF compared with rabbits exposed to BSA. 5. These results suggest that in the rabbit, PAF-induced bronchial hyperresponsiveness at 24 h is associated with airways inflammation and is dependent upon platelet activation, but is not related to changes in airway smooth muscle function.
Coyle
A J
AJ
Department of Pharmacology, King's College, University of London.
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D000336:Aerosols; D000818:Animals; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D001980:Bronchi / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid; D002217:Carbachol / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008170:Lung Compliance / Q000187:drug effects; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010976:Platelet Count; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000276:immunology
D000336:Aerosols; D008688:Methacholine Compounds; D010972:Platelet Activating Factor; D012710:Serum Albumin, Bovine; D006632:Histamine; D002217:Carbachol